Expression And Significance Of TRB3 In The Brain Of APP/PS1 Transgenic Mice

BackgroundAlzheimer’s disease (AD) is a central nervous degenerative disease which is characterized by progressive cognitive decline and behavioral impairment. Its main clinical manifestations include memory decline, visual spatial disorientation, aphasia, apraxia and agnosia. The underlying mechanism of Alzheimer’s disease still remains complicated and unclear. It is widely confirmed that Alzheimer’s disease has a close relation with endoplasmic reticulum stress (ERS), and ERS is considered as an important pathogenesis of Alzheimer’s disease. TRB3 (also called TRIB3, NIPK, SINK, or SKIP3) is one of the family members of mammalian homologous protein of Drosophila Tribbles, and its gene was found in an experiment of neuronal apoptosis in 1999. TRB3 is a critical factor in ERS, and its inducement can be found when ERS occurs with different reasons. ERS can stimulate the ATF4-CHOP pathway where TRB3 is at the downstream of it. TRB3 is a target and mediates the apoptosis of the ATF4-CHOP pathway. However, there is no report of TRB3 expressions in Alzheimer’s disease.ObjectiveTo explore expressions of endoplasmic reticulum stress factor TRB3 in the brain of APP/PS1 transgenic mice of different months, and to clarify its relation with the evolvements of Alzheimer’s disease.Methods1. Experiment group3 and 7 months old APP/PS1 transgenic mice were used in this study, and wild type (WT) C57/BL6J mice were used as control group. Mice were divided into 3 months old WT group,3 months old APP/PS1 group,7 months old WT group and 7 months old APP/PS1 group, and each group had 10 mice.2. Morris Water MazeBehavioral changes of mice were studied by Morris Water Maze, and it includes place navigation test and spatial probe test. It can measure mice latency time, mice crossing numbers of former platform’s place and mice residence time at the quadrant of former platform.3. Detection of TRB3When behavioral test was completed, mice were executed. Expressions of TRB3 in the brain were studied by immunohistochemistry and Western blotting.Results1. Behavioral test resultsCompared with WT mice of same months, there were no significant changes of mice latency time, mice crossing numbers and mice residence time in 3 months old APP/PS1 mice (P□0.05), and compared with WT mice of same months, there were significant changes of mice latency time, mice crossing numbers and mice residence time in 7 months old APP/PS1 mice (P<0.05). This result indicated that spatial learning and memory decline was found in 7 months old APP/PS1 mice, which was the primary manifestation of Alzheimer’s disease.2. TRB3 expressions in different mice groups2.1 Immunohistochemistry resultsTRB3 was mainly expressed in brain cortex. Compared with WT mice of same months, TRB3 expressions increased significantly in the brain of both 3 and 7 months old APP/PS1 mice (P<0.05), and 7 months old APP/PS1 mice had more TRB3 expressions than 3 months old APP/PS1 mice in the brain (P<0.05).2.2 Western blotting resultsTRB3 expressions were basically identical to immunohistochemistry results in mice groups of different months and genotypes. Compared with WT mice of same months, TRB3 expressions increased significantly in the brain of both 3 and 7 months old APP/PS1 mice (P<0.05), and 7 months old APP/PS1 mice had more TRB3 expressions than 3 months old APP/PS1 mice in the brain (P<0.05).ConclusionsTRB3 expressions increase in the brain of APP/PS1 transgenic mice and its increase may be related to the evolvement of Alzheimer’s disease.